Miami Holistic
CenterRole of acupuncture in the treatment of female infertility
Role of acupuncture in the treatment of female infertility
Raymond Chang, M.D.[a,b] Pak H. Chung, M.D.[b] and Zev Rosenwaks,
M.D.[c]
The Institute of East-West Medicine and the Center for
Reproductive Medicine and Infertility, Weill Medical College of
Cornell University, New York, New York
FERTILITY AND STERILITY® VOL. 78, NO. 6, DECEMBER 2002
Copyright ©2002 American Society for Reproductive Medicine
Published by Elsevier Science Inc., Printed on acid-free paper
in U.S.A.
Objective: To review existing scientific rationale and clinical
data in the utilization of acupuncture in the treatment of
female infertility.
Design: A MEDLINE computer search was performed to identify
relevant articles.
Result(s): Although the understanding of acupuncture is based on
ancient medical theory, studies have suggested that certain
effects of acupuncture are mediated through endogenous opioid
peptides in the central nervous system, particularly
ß-endorphin. Because these neuropeptides influence gonadotropin
secretion through their action on GnRH, it is logical to
hypothesize that acupuncture may impact on the menstrual cycle
through these neuropeptides. Although studies of adequate
design, sample size, and appropriate control on the use of
acupuncture on ovulation induction are lacking, there is only
one prospective randomized controlled study examining the
efficacy of acupuncture in patients undergoing IVF. Besides its
central effect, the sympathoinhibitory effects of acupuncture
may impact on uterine blood flow.
Conclusion(s): Although the definitive role of acupuncture in
the treatment of female infertility is yet to be established,
its potential impact centrally on the
hypothalamic-pituitary-ovarian axis and peripherally on the
uterus needs to be systemically examined. Prospective randomized
controlled studies are needed to evaluate the efficacy of
acupuncture in the female fertility treatment. (Fertil Steril®
2002;78:1149-53. ©2002 by American Society for Reproductive
Medicine.)
Key Words: Acupuncture, female infertility, in vitro
fertilization
Acupuncture as a therapeutic intervention has been extensively
studied and is increasingly practiced in the United States. A
recent survey of acupuncture released by an NIH Consensus
Development panel (1) indicated that although there are inherent
problems of design, sample size, and appropriate controls in the
acupuncture literature, promising data exist for the use of
acupuncture in treating nausea and vomiting (2), postoperative
pain (3-5), addiction (6-9), and general pain syndromes (10-12).
As a medical technique, acupuncture has also been reported as an
adjunct in the treatment of various gynecologic problems
(13-15).
Although conventional treatment options for female infertility
have been well established, there have been few systematic
reviews of complementary or alternative approaches to the
treatment of infertility. In light of an increasing trend in the
use of complementary and alternative medicine (16) and common
inquiry and utilization of such approaches by patients suffering
from infertility, we intend to review the existing scientific
rationale and clinical data based on which acupuncture may exert
an influence on the outcome of female fertility.
In examining the potential usefulness of acupuncture in
enhancing female fertility, it is appropriate first to give some
theoretical background for acupuncture. Although the theory of
acupuncture stems from underlying traditional Chinese medicine
premises that would define etiologies for infertility in terms
of energy disturbance of imbalances, or organ deficiencies and
excesses, we intend to review the existing literature by
examining modern medical aspects of the central and peripheral
modes of action of acupuncture as they impact on the
hypothalamic-pituitary-ovarian axis and the pelvic organs,
respectively. Moreover, the effect of acupuncture on anxiety and
stress and ensuing potential indirect effects on female
fertility will also be discussed.
Background
Acupuncture is the manipulation of thin metallic needles
inserted into anatomically defined locations on the body to
affect bodily function. The US Food and Drug Administration has
recently removed acupuncture needles from the category of
experimental medical devices and now regulates them just like it
does other devices, such as surgical scalpels and hypodermic
needles, under good manufacturing practices and single-use
standard of sterility (1).
The general theory of acupuncture is based on the premise that
there are patterns of energy flow (Qi) through the body, which
are essential for health. Disruption of this flow is believed to
be responsible for disease. Acupuncture can correct imbalances
of flow at identifiable points close to the skin.
According to the proposed international acupuncture nomenclature
by The World Health Organization in 1991 (17), the meridian
system consists of 20 meridians interconnecting about 400
acupoints. These acupoints correspond to specific areas on the
surface of the body, which demonstrate higher electrical
conductance because of the presence of higher density of gap
junctions along cell borders. They act as converging points (or
sinks) for electromagnetic fields. A higher metabolic rate,
temperature, and calcium ion concentration, are also observed at
these points. In principle, positive (anode) pulse stimulation
of a point inhibits the organ function, whereas negative
(cathode) pulse stimulation enhances that function (18). This
forms the basis of electroacupuncture, which applies small
electrical needles inserted in specific acupoints.
Effects of acupuncture on the hypothalamic-pituitary-ovarian
axis and menstrual cycle
Although traditional Chinese medicine understanding of
acupuncture is based on ancient medical theory, a modern and
scientific neuroendocrine perspective has begun to evolve in the
past two decades. Mayer et al. (19) first reported that
acupuncture analgesia was induced through endorphin production
and antagonized by the narcotic antagonist naloxone. Other
studies similarly suggested that certain effects of acupuncture
are mediated through the nervous system, within which
ß-endorphin and other neuropeptides have been implicated
(20-22).
Acupuncture was shown by Petti et al. (20) to cause a
significant increase in ß-endorphin levels during treatment,
which lasted for up to 24 hours. ß-endorphin is derived from its
precursor protein pro-opiomelanocortin, which is present in
abundant amounts in neuronal cells of the arcuate nucleus of the
hypothalamus, pituitary, medulla, and in peripheral tissues
including intestines and ovaries (23-25). Pro-opiomelanocortin
cleaves to form adrenocorticotropic hormone and ß-lipoprotein.
Further cleavage of ß-lipoprotein yields neuropeptides including
ß-endorphin. Aleem et al. (26, 27) demonstrated the presence of
immunoreactive ß-endorphin in follicular fluids of both normal
and polycystic ovaries.
The influence on gonadotropin secretion and the menstrual cycle
by endogenous opioid peptides is believed to be mediated by
their action on GnRH secretion (28). The hypothalamic
ß-endorphin center and the GnRH pulse generator, in fact, are
both situated within the arcuate nucleus. Quigley et al. (29)
first reported an increased opioid inhibition of LH secretion in
hyperprolactinemic patients with pituitary microadenomas. Ching
(30) and Orstead and Spics (31), respectively, showed that
opioid peptides suppress GnRH release in rats and rabbits.
The role of these neuropeptides, including ß-endorphin, in the
regulation of GnRH secretion in humans has recently been
reviewed by Kalra et al. (32) and Pau and Spies (33). Rossmanith
et al. (34) demonstrated the role of opioid peptides in the
initiation of the mid-cycle LH surge in normal cycling women.
Meanwhile, measurement of ß-endorphin in ovarian follicular
fluid of healthy ovulatory women revealed much higher levels
than that in circulating plasma (35). The highest level of
ß-endorphin was noted to be in the preovulatory follicle.
Because acupuncture treatment impacts on ß-endorphin levels,
which in turn affect GnRH secretion and the menstrual cycle, it
is logical to hypothesize that acupuncture may influence
ovulation and fertility. Animal studies have revealed that
acupuncture treatment normalized GnRH secretion and affected
peripheral gonadotropin levels (36, 37). Various investigators
have shown that in normally ovulatory or anovulatory women,
acupuncture also influenced plasma levels of FSH, LH, E2, and P
(38-40). Acupuncture as a surrogate for hCG in ovulation
induction was successfully used by Cai (41). Chen and Yu (42)
showed that electroacupuncture normalized they
hypothalamic-pituitary-ovarian axis, and in another study Chen
(43) reported that 6 of 13 anovulatory cycles responded to
acupuncture treatment.
A series published from the University of Heidelberg in Germany
(44) used auricular acupuncture on 45 infertile women suffering
from ovulatory dysfunction such as oligomenorrhea and luteal
phase defect. The control group received medical treatment
including bromocriptine, dexamethasone, levothyroxine,
clomiphene citrate (CC), and gonadotropin. Although the
investigators concluded that resumption of ovulatory cycles
occurred significantly more often in the acupuncture group
compared to the control group, pregnancy rates were not
different between the two groups. However, interpretation of
study data was very difficult due to the heterogeneity of the
patient population and treatment modalities. Moreover, seven
pregnancies in the acupuncture group were actually achieved with
hormone treatment 6 months after acupuncture was stopped.
Another study by Stenver-Victorin et al. (45) evaluated the use
of electroacupuncture for ovulation induction on 24 oligo/amenorrheic
women with polycycstic ovarian syndrome (PCOS). The percentage
of ovulatory cycles in all subjects was shown to improve from
15% (in a total of 3 months before treatment) to 66% up to 3
months after treatment. Responsive patients were noted to have
significantly lower body mass index (BMI), waist-to-hip
circumference ratio, serum T concentration, serum T/sex
hormone-binding globulin ratio, and serum basal insulin level.
They suggested that, in these selected patients with PCOS,
acupuncture could be considered as an alternative or adjunct to
pharmacological ovulation induction.
A recent prospective randomized controlled study by Paulus et
al. (46) compared pregnancy rates in a total of 160 patients
undergoing IVG. Acupuncture was performed in 80 patients 25
minutes before and after ET. After controlling confounding
variables, clinical pregnancy rate for the acupuncture group
(42.5%) was significantly higher than the control group (26.3%).
Peripheral effects of acupuncture
In addition to the central modulation of the
hypothalamic-pituitary-ovarian axis, the effects of acupuncture
on the autonomic nervous system have been well documented (47).
In the early 1980s, Yao et al. (48) reported long-lasting
cardiovascular depression induced by acupuncture stimulation of
the sciatic nerve in unanesthetized hypertensive rats. In the
human, acupuncture was also shown to be sympathoinhibitory.
After acupuncture, sympathetic nerve activity as measured by
norepinephrine level, skin temperature, blood pressure, and pain
tolerance threshold was shown to be decreased (49).
Endometrial thickness, morphology, and uterine artery blood flow
have been implicated as important parameters for success of
implantation of human embryos (50-57). Despite conflicting
results in the utilization of these parameters during various
stages of treatment to predict outcome in IVF, it is generally
believed that adequate endometrial thickness is required to
optimize pregnancy rate. Because endometrial thickness is a
function of uterine artery blood flow, Sher and Fisch (58)
reported a novel method of using vaginal sildenafil in an
attempt to improve uterine artery blood flow and endometrial
development in patients undergoing IVF.
With its central sympathoinhibitory effect, acupuncture may
contribute to reduce uterine artery impedance and therefore,
increase blood flow to the uterus. In fact, Sterner-Victorin et
al. (59) demonstrated this when they performed acupuncture in 10
infertile women who were down-regulated by GnRH analog to avoid
the effect of endogenous hormone on the uterine artery blood
flow.
Pulsatility index in the uterine artery and skin temperature (on
the forehead and lumbosacral area) were evaluated in three time
periods-before, right after, and 2 weeks after acupuncture
treatment (twice a week for 4 weeks). Pulsatility index and skin
temperatures were found to be significantly decreased and
increased, respectively, both right after and 14 days after
acupuncture treatment. This effect was hypothesized to be caused
by central inhibition of sympathetic activity.
Acupuncture and stress reduction
It has been well documented that infertility causes stress
(60-65), and stress reduction may, in turn, improve fertility
(66). However, the relationship between stress and infertility
is that of a vicious cycle. Social stigmatization, decreased
self-esteem, unmet reproductive potential of sexual
relationship, physical and mental burden of treatment, and the
lack of control on treatment outcome are just some of the
factors that can lead to psychological stress in any couple
pursuing infertility treatment. In turn, stress may lead to the
release of stress hormones and influence mechanisms responsible
for a normal ovulatory menstrual cycle through its impact on the
hypothalamic-pituitary-ovarian axis.
The use of acupuncture for reducing anxiety and stress possibly
through its sympathoinhibitory property and impact on
ß-endorphin levels has been reviewed (67, 68), and the efficacy
of acupuncture in depression has also been studied (69). Because
the pharmacological side effects of anxiolytic and
antidepressant drugs on infertility treatment outcome are
largely unknown, acupuncture may provide an excellent
alternative for stress reduction in women undergoing infertility
treatment.
Discussion
The practice of acupuncture to treat identifiable patho-physiological
conditions has been a subject of intense research. The
underlying physiologic mechanisms of acupuncture such as the
release of opioids and other peptides in the central peripheral
nervous system, and its inhibition of the sympathetic nervous
system have been increasingly established. Promising results
from credible trials have emerged for the use of acupuncture in
treating various pain syndromes, substance abuse, and
chemotherapy-induced nausea and vomiting.
Although the definitive role of acupuncture in the treatment of
female infertility is yet to be established, its neuroendocrine
effect on the hypothalamic-pituitary-ovarian axis and the
preliminary clinical data reviewed here justifies further
clinical trials to systematically examine the efficacy of
acupuncture in treating various conditions related to female
infertility such as ovulatory dysfunction associated with PCOS.
The peripheral impact of acupuncture in improving uterine artery
blood flow and hence endometrial thickness also provides
encouraging data regarding its potential positive effect on
implantation.
Whether these potential beneficial effects of acupuncture on the
reproductive system can be translated into improving infertility
treatment outcomes will eventually mandate randomized controlled
studies of adequate design. Because acupuncture is nontoxic and
relatively affordable, its indications as an adjunct in assisted
reproduction or as an alternative for women who are intolerant,
ineligible, or contraindicated for conventional hormone
induction of ovulation deserves serious research and
exploration.
Appropriate training, credentialing, and certification of
acupuncture practitioners by state agencies can facilitate the
integration of acupuncture into the treatment of female
infertility, and healthcare in general. The NIH Consensus
Conference (1) agreed that this is necessary to allow the public
and other health practitioners to identify qualified acupuncture
practitioners. With the help of the US Department of Education,
issues of training and licensure of non-physician and physician
practitioners have been addressed. There is sufficient evidence
to acupuncture's value to expand its use into conventional
medicine and treatment of female infertility, and to encourage
further studies of its underlying mechanisms as well as to
establish its clinical value.